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NCT Number: NCT05165706

Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance

This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.

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Key information

Conditions

Diabetes Mellitus, Type 2 Body Weight Diabetes Mellitus Diet Modification Digestive System Diseases Endocrine System Diseases Fatty Liver Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Liver Diseases Metabolic Diseases Non-alcoholic Fatty Liver Disease Nonalcoholic Fatty Liver Nonalcoholic Steatohepatitis Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms PreDiabetes Prediabetic State Signs and Symptoms

Age range

35 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Stanford University

Stanford, California, 94305, United States

Location status: Recruiting

Location contact

Dalia Perelman, MS, RD

CONTACT

[email protected]

Ekrem M Ayhan, BS

CONTACT

[email protected]

908-619-5381

Tracey L McLaughlin, MD, MS

PRINCIPAL_INVESTIGATOR

About this study

Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 35-65
  • BMI 25-35 kg/m2
  • Stable body weight
  • Nondiabetic

Exclusion criteria

Patients with;

  • diabetes
  • major organ disease
  • history of liposuction or bariatric surgery
  • active eating or psychiatric disorder
  • pregnancy or lactation, heavy alcohol use
  • recent change in weight (over the past 12 weeks)
  • use of weight loss medication, statins, or oral steroids

Clinical screening exclusions;

  • hematocrit < 33%
  • fasting glucose >/= 126 mg/dL
  • blood pressure >160/100 mmHg

Treatment and study plan

Dietary Intervention Mediterranean Low Carbohydrate Diet

Behavioral

Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Dietary Intervention Standard Low Carbohydrate Diet

Behavioral

Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Dietary Intervention Standard Low Fat Diet

Behavioral

Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Primary outcomes

  1. Change from baseline on the 2-stage Steady State Plasma Glucose test

    Time frame: Peak weight (4 weeks)

    Compare direct measurement of insulin sensitivity after 4 week diet and weight intervention

  2. Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio

    Time frame: Peak weight (4 weeks)

    Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 4 week diet and weight intervention

  3. Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition

    Time frame: Peak weight (4 weeks)

    Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 4 week diet and weight intervention

  4. Change from peak weight on the 2-stage Steady State Plasma Glucose test

    Time frame: Post-weight loss (8 weeks)

    Compare direct measurement of insulin sensitivity after 8 week diet and weight intervention

  5. Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio

    Time frame: Post-weight loss (8 weeks)

    Compare measurement of abdominal V:S fat volume via computed tomography (CT) after 8 week diet and weight intervention

  6. Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition

    Time frame: Post-weight loss (8 weeks)

    Compare measurement of liver fat content via magnetic resonance spectroscopy (MRS) after 8 week diet and weight intervention

  7. Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA

    Time frame: Baseline

    Compare adipose tissue transcripts such as known MODY transcription factors, defensin chemokine receptors, and platelet activation factors measured by PCR between participants identified as Insulin sensitive (IS) and Insulin resistant (IR) using the 2-stage Steady State Plasma Glucose test.

  8. Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay

    Time frame: Baseline

    Compare plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay between participants identified as Insulin Sensitive (IS) and Insulin Resistant (IR) using the 2-stage Steady State Plasma Glucose test.

  9. Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay

    Time frame: Peak Weight (4 weeks)

    Compare intra-personal levels of plasma inflammatory cytokines as measured by Luminex immunoassay after 4 week diet and weight intervention

Study contacts

Contact information is provided by the study sponsor or research team.

Dalia Perelman, MS, RD

CONTACT

[email protected]

Ekrem M Ayhan, BS

CONTACT

[email protected]

908-619-5381

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Dec 21, 2021
Registry last updated
Dec 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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